Carboplatin, Paclitaxel, and Everolimus in Treating Patients With Previously Untreated Cancer of Unknown Primary

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00936702
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 46
• Locations: 141
• Arm: 1
• Duration (Months): 47
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well carboplatin given together with paclitaxel and everolimus works in treating patients with previously untreated cancer of unknown primary.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma of Unknown Primary Origin	Drug: carboplatin; Drug: everolimus; Drug: paclitaxel	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Evaluate the response rate in patients with previously untreated cancer of unknown primary treated with the combination of carboplatin, paclitaxel, and everolimus.

Secondary

• Assess time to progression, overall survival, duration of response, and time to treatment failure in patients treated with this regimen.

• Determine adverse events of this regimen in these patients.

• Perform descriptive correlative studies to determine response of specific tumor types, identified by the Origin-FFPE test, to this regimen.

OUTLINE: This is a multicenter study.

Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive oral everolimus once daily on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients' tumor tissue samples from the most recent biopsy are analyzed for correlative studies, including gene expression profiling by Origin-FFPE test.

After completion of study therapy, patients are followed up every 3 months until disease progression, and then every 6 months for up to 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Carboplatin (CBDCA), Paclitaxel (TAXOL), and Everolimus (RAD001) in Previously Untreated Patients With Measurable Disease With Cancer of Unknown Primary (CUP)
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (carboplatin, paclitaxel, and everolimus) Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin; Given IV; Drug: everolimus; Given PO; Drug: paclitaxel; Given IV

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Confirmed Tumor Responses [First 6 Cycles of treatment (an average of 6 months)]

   Confirmed tumor response was defined to be either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;

Secondary Outcome Measures

1. Overall Survival [Time from registration to death or last follow-up (up to 3 years)]

   Overall survival was defined as the time from study enrollment to the time of death from any cause or last follow-up.

2. Progression-free Survival [Time from registration to the disease progression or death (up to 3 years)]

   The progression-free survival (PFS) was defined as the time from date of registration to the documentation of disease progression or death as a result of any cause, whichever comes first.

3. Duration of Response [Up to 3 years]

   Duration of response was defined for all evaluable participants who have achieved an objective response as the date at which the participant's objective status is first noted to be either CR or PR to the date progression is documented.

4. Time to Treatment Failure [Up to 3 years]

   Time to treatment failure was defined to be the time from the date of registration to the date at which the participant is removed from treatment due to progression, adverse events, or refusal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Histological confirmation of metastatic adenocarcinoma, poorly differentiated non-small cell carcinoma, or poorly differentiated squamous carcinoma

• Adequate FFPE tissue or re-biopsy planned after registration but prior to treatment

• Measurable disease as defined; for patients having only lesions measuring at least 1 cm to =< 2 cm must use spiral computed tomography (CT) imaging for both pre- and post-treatment tumor assessments; disease that has received prior radiation (performed for palliative reasons) cannot be used for measurable disease

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Hemoglobin (Hgb) >= 9.0 g/dL

• Absolute neutrophil count (ANC) >= 1,500/uL

• Platelet count >= 100,000/uL

• Total bilirubin =< upper limits of normal (ULN); if liver metastases are present, total bilirubin =< 2 x ULN

• Aspartate aminotransferase (AST) =< 2.5 x ULN; if liver metastases are present, AST =< 5 x ULN

• Creatinine =< 1.25 x ULN; if > 1.25 x ULN calculated creatinine clearance must be >= 60 ml/min

• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

• Provide informed written consent

• Willingness to return to NCCTG enrolling institution for follow-up

• Willingness to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study

Exclusion Criteria

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception; note: adequate contraception must be used throughout the trial and for 8 weeks after the last dose of RAD001, by both sexes

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• History of any of the following:

• Known to be human immunodeficiency virus (HIV) positive

• Known prior/current history of hepatitis related to hepatitis B or hepatitis C

• Uncontrolled intercurrent illness including, but not limited to the following:

• Ongoing or active infection (acute or chronic)

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Severely impaired lung function

• Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN (note: optimal glycemic control should be achieved before starting trial therapy)

• Liver disease such as cirrhosis or severe hepatic impairment

• Psychiatric illness/social situations that would limit compliance with study requirements

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 4 weeks prior to registration

• Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer

• Untreated brain metastases; NOTE: patients with treated, stable brain metastases for at least 12 weeks prior to study entry are eligible for enrollment

• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

• Active, bleeding diathesis

• Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed

• Currently on enzyme inducing anti-convulsants (EIACs) or other strong inducers or strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)

• Current use of warfarin (Coumadin); EXCEPTION: current use of low-molecular weight heparin is allowed

• Known to be HIV positive

• Inoculated with live attenuated vaccines =< 2 weeks prior to registration; note: close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines

• =< 4 weeks from major surgery; note: for this study, diagnostic laparoscopy (without other intervention) and/or biopsies (needle aspirate, core biopsy, open biopsy, etc.) are not considered major surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
2	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
3	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
4	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
5		Moline	Illinois	United States	61265
6	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
7	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana	United States	46514
8	Elkhart General Hospital	Elkhart	Indiana	United States	46515
9	St. Francis Hospital Cancer Care Services	Indianapolis	Indiana	United States	46237
10	Howard Community Hospital	Kokomo	Indiana	United States	46904
11	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
12	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana	United States	46545-1470
13	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
14	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana	United States	46563
15	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
16	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
17	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
18	Michiana Hematology Oncology PC - La Porte	Westville	Indiana	United States	46391
19	McFarland Clinic, PC	Ames	Iowa	United States	50010
20		Bettendorf	Iowa	United States	52722
21	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
22	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
23	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
24	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
25	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
26	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
27	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
28	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
29	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
30	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
31	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
32	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
33	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
34	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
35	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
36	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
37	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
38	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
39	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
40	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
41	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67901
42	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
43	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
44	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
45	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
46	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
47	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
48	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
49	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
50	CCOP - Wichita	Wichita	Kansas	United States	67214
51	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
52	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
53	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
54	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
55	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
56	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
57	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
58	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
59	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
60	Hurley Medical Center	Flint	Michigan	United States	48503
61	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
62	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
63	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
64	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
65	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
66	Foote Memorial Hospital	Jackson	Michigan	United States	49201
67	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
68	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
69	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
70	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
71	Mercy General Health Partners	Muskegon	Michigan	United States	49444
72	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
73	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
74	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
75	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
76	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
77	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
78	Munson Medical Center	Traverse City	Michigan	United States	49684
79	St. John Macomb Hospital	Warren	Michigan	United States	48093
80	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
81	Essentia Health - Duluth Clinic	Duluth	Minnesota	United States	55805-1983
82	CCOP - Duluth	Duluth	Minnesota	United States	55805
83	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
84	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
85	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65804
86	St. John's Regional Health Center	Springfield	Missouri	United States	65804
87	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
88	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
89	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
90	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
91	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
92	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
93	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
94	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
95	St. Peter's Hospital	Helena	Montana	United States	59601
96	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
97	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
98	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
99	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
100	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
101	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
102	MeritCare Broadway	Fargo	North Dakota	United States	58102
103	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
104	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
105	Grandview Hospital	Dayton	Ohio	United States	45405
106	Good Samaritan Hospital	Dayton	Ohio	United States	45406
107	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
108	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
109	CCOP - Dayton	Dayton	Ohio	United States	45420
110	Community Cancer Center	Elyria	Ohio	United States	44035
111	Hematology Oncology Center	Elyria	Ohio	United States	44035
112	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
113	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
114	Wayne Hospital	Greenville	Ohio	United States	45331
115	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
116	Lima Memorial Hospital	Lima	Ohio	United States	45804
117	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
118	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
119	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
120	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
121	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
122	Toledo Hospital	Toledo	Ohio	United States	43606
123	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
124	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
125	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
126	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
127	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
128	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
129	Fulton County Health Center	Wauseon	Ohio	United States	43567
130	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
131	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
132	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
133	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
134	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
135	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
136	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
137	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
138	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
139	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
140	St. Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
141	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Matthew P. Goetz, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00936702
• Other Study ID Numbers: NCCTG-N0871; NCI-2011-01926; CDR0000643361
• First Posted: Jul 10, 2009
• Last Update Posted: Mar 21, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Alliance for Clinical Trials in Oncology: Newly Diagnosed Carcinoma of Unknown Primary Origin; Squamous Cell Carcinoma of Unknown Primary Origin; Undifferentiated Carcinoma of Unknown Primary; newly diagnosed carcinoma of unknown primary
• Additional relevant MeSH terms: Carcinoma; Neoplasms, Unknown Primary; Paclitaxel; Carboplatin; Everolimus

Study Results

Participant Flow

Recruitment Details	Forty-six participants with centrally confirmed cancer of unknown primary site were enrolled between October 2009 and October 2012. The trial was closed before the target sample size of 50 was reached, because a sufficient number of confirmed responses had occurred to meet the primary endpoint.

Arm/Group Title	Treatment (Carboplatin, Paclitaxel, and Everolimus)
Arm/Group Description	Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
Period Title: Overall Study
STARTED	46
COMPLETED	0
NOT COMPLETED	46

Baseline Characteristics

Arm/Group Title	Treatment (Carboplatin, Paclitaxel, and Everolimus)
Arm/Group Description	Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
Overall Participants	46
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	28 60.9%
Male	18 39.1%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0=Asymptomatic and fully active	25 54.3%
1=Symptomatic and fully ambulatory	15 32.6%
2=Symptomatic and ambulatory	6 13%
Histologic diagnosis (Count of Participants)
Adenocarcinoma	36 78.3%
Poorly differentiated nonsmall-cell carcinoma	5 10.9%
Poorly differentiated squamous carcinoma	1 2.2%
Other	4 8.7%
Histologic grade (Count of Participants)
Well	1 2.2%
Moderate	8 17.4%
Poor	28 60.9%
Undifferentiated, anaplastic	8 17.4%
Not Available	1 2.2%
Predominant location of disease (Count of Participants)
Liver	18 39.1%
Lung	10 21.7%
Soft tissue	9 19.6%
Bone	3 6.5%
Other	6 13%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Confirmed Tumor Responses
Description	Confirmed tumor response was defined to be either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;
Time Frame	First 6 Cycles of treatment (an average of 6 months)

Outcome Measure Data

Analysis Population Description

All participants except one who was deemed ineligible (treated prior to registration).

Arm/Group Title	Treatment (Carboplatin, Paclitaxel, and Everolimus)
Arm/Group Description	Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
Measure Participants	45
Number (95% Confidence Interval) [percentage of participants]	36 78.3%

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from study enrollment to the time of death from any cause or last follow-up.
Time Frame	Time from registration to death or last follow-up (up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants except one who was deemed ineligible (treated prior to registration).

Arm/Group Title	Treatment (Carboplatin, Paclitaxel, and Everolimus)
Arm/Group Description	Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
Measure Participants	45
Median (95% Confidence Interval) [months]	10.1

3. Secondary Outcome

Title	Progression-free Survival
Description	The progression-free survival (PFS) was defined as the time from date of registration to the documentation of disease progression or death as a result of any cause, whichever comes first.
Time Frame	Time from registration to the disease progression or death (up to 3 years)

Outcome Measure Data

Analysis Population Description

All participants except one who was deemed ineligible (treated prior to registration).

Arm/Group Title	Treatment (Carboplatin, Paclitaxel, and Everolimus)
Arm/Group Description	Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
Measure Participants	45
Median (95% Confidence Interval) [months]	4.1

4. Secondary Outcome

Title	Duration of Response
Description	Duration of response was defined for all evaluable participants who have achieved an objective response as the date at which the participant's objective status is first noted to be either CR or PR to the date progression is documented.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All eligible participants who have achieved an objective response at which the participant's objective status is first noted to be either CR or PR.

Arm/Group Title	Treatment (Carboplatin, Paclitaxel, and Everolimus)
Arm/Group Description	Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
Measure Participants	16
Median (95% Confidence Interval) [months]	5.8

5. Secondary Outcome

Title	Time to Treatment Failure
Description	Time to treatment failure was defined to be the time from the date of registration to the date at which the participant is removed from treatment due to progression, adverse events, or refusal.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All participant who has been removed from treatment due to progression, adverse events, or refusal.

Arm/Group Title	Treatment (Carboplatin, Paclitaxel, and Everolimus)
Arm/Group Description	Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
Measure Participants	40
Median (95% Confidence Interval) [months]	3.1

Adverse Events

Time Frame	Up to 3 years
Arm/Group Title	Treatment (Carboplatin, Paclitaxel, and Everolimus)
Arm/Group Description	Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15.
All Cause Mortality
	Treatment (Carboplatin, Paclitaxel, and Everolimus)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Carboplatin, Paclitaxel, and Everolimus)
	Affected / at Risk (%)	# Events
Total	21/46 (45.7%)
Blood and lymphatic system disorders
Hemoglobin decreased	5/46 (10.9%)	8
Cardiac disorders
Cardiac disorder	1/46 (2.2%)	1
Sinus tachycardia	1/46 (2.2%)	1
Gastrointestinal disorders
Abdominal distension	1/46 (2.2%)	1
Abdominal pain	2/46 (4.3%)	2
Constipation	1/46 (2.2%)	1
Diarrhea	3/46 (6.5%)	3
Dysphagia	1/46 (2.2%)	1
Nausea	1/46 (2.2%)	1
Vomiting	1/46 (2.2%)	1
General disorders
Fatigue	1/46 (2.2%)	1
Infections and infestations
Abdominal infection	1/46 (2.2%)	1
Pneumonia	1/46 (2.2%)	2
Sepsis	2/46 (4.3%)	2
Upper respiratory infection	1/46 (2.2%)	1
Investigations
Alkaline phosphatase increased	1/46 (2.2%)	1
Leukocyte count decreased	5/46 (10.9%)	5
Neutrophil count decreased	15/46 (32.6%)	18
Platelet count decreased	8/46 (17.4%)	8
Metabolism and nutrition disorders
Anorexia	1/46 (2.2%)	1
Dehydration	2/46 (4.3%)	2
Serum magnesium decreased	1/46 (2.2%)	1
Serum potassium decreased	1/46 (2.2%)	1
Serum sodium decreased	2/46 (4.3%)	2
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb	1/46 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/46 (2.2%)	1
Hypoxia	1/46 (2.2%)	1
Respiratory disorder	1/46 (2.2%)	1
Vascular disorders
Thrombosis	2/46 (4.3%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Carboplatin, Paclitaxel, and Everolimus)
	Affected / at Risk (%)	# Events
Total	45/46 (97.8%)
Blood and lymphatic system disorders
Febrile neutropenia	2/46 (4.3%)	2
Hemoglobin decreased	44/46 (95.7%)	243
Eye disorders
Extraocular muscle paresis	1/46 (2.2%)	1
Eye disorder	1/46 (2.2%)	1
Gastrointestinal disorders
Abdominal pain	3/46 (6.5%)	4
Ascites	2/46 (4.3%)	6
Constipation	2/46 (4.3%)	2
Diarrhea	21/46 (45.7%)	48
Dyspepsia	1/46 (2.2%)	1
Ear, nose and throat examination abnormal	2/46 (4.3%)	3
Mucositis oral	3/46 (6.5%)	3
Nausea	32/46 (69.6%)	93
Vomiting	15/46 (32.6%)	25
General disorders
Edema limbs	1/46 (2.2%)	3
Fatigue	20/46 (43.5%)	52
Fever	3/46 (6.5%)	4
Pain	2/46 (4.3%)	8
Immune system disorders
Cytokine release syndrome	1/46 (2.2%)	1
Hypersensitivity	12/46 (26.1%)	15
Infections and infestations
Bladder infection	1/46 (2.2%)	1
Pharyngitis	2/46 (4.3%)	2
Pneumonia	1/46 (2.2%)	1
Sinusitis	1/46 (2.2%)	1
Skin infection	4/46 (8.7%)	4
Tooth infection	1/46 (2.2%)	1
Upper respiratory infection	1/46 (2.2%)	1
Urinary tract infection	1/46 (2.2%)	1
Investigations
Activated partial thromboplastin time prolonged	1/46 (2.2%)	1
Alanine aminotransferase increased	1/46 (2.2%)	2
Alkaline phosphatase increased	4/46 (8.7%)	10
Aspartate aminotransferase increased	3/46 (6.5%)	4
Forced expiratory volume decreased	1/46 (2.2%)	1
Leukocyte count decreased	40/46 (87%)	205
Lymphocyte count decreased	3/46 (6.5%)	8
Neutrophil count decreased	38/46 (82.6%)	169
Platelet count decreased	31/46 (67.4%)	174
Serum cholesterol increased	1/46 (2.2%)	1
Weight gain	1/46 (2.2%)	1
Weight loss	2/46 (4.3%)	4
Metabolism and nutrition disorders
Anorexia	30/46 (65.2%)	93
Blood glucose increased	2/46 (4.3%)	2
Dehydration	5/46 (10.9%)	9
Serum albumin decreased	2/46 (4.3%)	4
Serum calcium decreased	1/46 (2.2%)	1
Serum calcium increased	1/46 (2.2%)	1
Serum magnesium decreased	1/46 (2.2%)	1
Serum phosphate decreased	1/46 (2.2%)	3
Serum potassium decreased	1/46 (2.2%)	1
Serum potassium increased	1/46 (2.2%)	1
Serum sodium decreased	3/46 (6.5%)	3
Serum triglycerides increased	2/46 (4.3%)	2
Musculoskeletal and connective tissue disorders
Arthritis	1/46 (2.2%)	1
Back pain	3/46 (6.5%)	3
Bone pain	3/46 (6.5%)	5
Joint pain	5/46 (10.9%)	10
Muscle weakness	1/46 (2.2%)	2
Muscle weakness lower limb	3/46 (6.5%)	3
Muscle weakness upper limb	1/46 (2.2%)	1
Myalgia	4/46 (8.7%)	20
Neck pain	1/46 (2.2%)	1
Pain in extremity	2/46 (4.3%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	1/46 (2.2%)	1
Nervous system disorders
Dizziness	1/46 (2.2%)	3
Neuralgia	1/46 (2.2%)	1
Peripheral motor neuropathy	1/46 (2.2%)	1
Peripheral sensory neuropathy	16/46 (34.8%)	46
Seizure	1/46 (2.2%)	1
Psychiatric disorders
Anxiety	2/46 (4.3%)	3
Confusion	1/46 (2.2%)	1
Insomnia	1/46 (2.2%)	1
Renal and urinary disorders
Glomerular filtration rate decreased	1/46 (2.2%)	1
Reproductive system and breast disorders
Erectile dysfunction	1/46 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/46 (2.2%)	1
Cough	2/46 (4.3%)	4
Dyspnea	5/46 (10.9%)	7
Pneumonitis	5/46 (10.9%)	7
Skin and subcutaneous tissue disorders
Alopecia	20/46 (43.5%)	73
Decubitus ulcer	1/46 (2.2%)	1
Dry skin	1/46 (2.2%)	1
Pruritus	2/46 (4.3%)	2
Rash acneiform	1/46 (2.2%)	2
Rash desquamating	17/46 (37%)	34
Vascular disorders
Hypotension	1/46 (2.2%)	4
Thrombosis	2/46 (4.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.